Oral tranexamic acid for an additional 24 hours postoperatively versus a single preoperative intravenous dose for reducing blood loss in total knee arthroplasty: results of a randomized controlled trial (TRAC-24)

Abstract

Aims In total knee arthroplasty (TKA), blood loss continues internally after surgery is complete. Typically, the total loss over 48 postoperative hours can be around 1,300 ml, with most occurring within the first 24 hours. We hypothesize that the full potential of tranexamic acid (TXA) to decrease TKA blood loss has not yet been harnessed because it is rarely used beyond the intraoperative period, and is usually withheld from ‘high-risk’ patients with a history of thromboembolic, cardiovascular, or cerebrovascular disease, a patient group who would benefit greatly from a reduced blood loss. Methods TRAC-24 was a prospective, phase IV, single-centre, open label, parallel group, randomized controlled trial on patients undergoing TKA, including those labelled as high-risk. The primary outcome was indirect calculated blood loss (IBL) at 48 hours. Group 1 received 1 g intravenous (IV) TXA at the time of surgery and an additional 24-hour postoperative oral regime of four 1 g doses, while Group 2 only received the intraoperative dose and Group 3 did not receive any TXA. Results Between July 2016 and July 2018, 552 patients were randomized to either Group 1 (n = 241), Group 2 (n = 243), or Group 3 (n = 68), and 551 were included in the final analysis. The blood loss did differ significantly between the two intervention groups (733.5 ml (SD 384.0) for Group 1 and 859.2 ml (SD 363.6 ml) for Group 2; mean difference -125.8 ml (95% confidence interval -194.0 to -57.5; p < 0.001). No differences in mortality or thromboembolic events were observed in any group. Conclusion These data support the hypothesis that in TKA, a TXA regime consisting of IV 1 g perioperatively and four oral 1 g doses over 24 hours postoperatively significantly reduces blood loss beyond that achieved with a single IV 1 g perioperative dose alone. TXA appears safe in patients with history of thromboembolic, cardiovascular, and cerebrovascular disease. Cite this article: Bone Joint J 2021;103-B(10):1595–1603.

The Optimal Dose, Efficacy and Safety of Tranexamic Acid and Epsilon‐Aminocaproic Acid to Reduce Bleeding in TKA: A Systematic Review and Bayesian Network Meta‐analysis

“…3 Rank of probability for less total blood loss after TKA 935 eligible studies reported TBL. 12,[24][25][26]28,29,32,33,36,37,40,43,44,[49][50][51][52][53][55][56][57]59 Network diagrams of comparisons on TBL are presented in Fig. 2A-C.…”

“…Transfusion rates of 31 studies 12,[24][25][26][27][28]30,[32][33][34][37][38][39][40][41][42][43][44]46,47,[49][50][51][52][53][55][56][57][58][59][60] were evaluated in the network. Network plots of comparisons on transfusion rates are shown in Fig.…”

Using tranexamic acid for an additional 24 hours postoperatively in hip and knee arthroplasty saves money: a cost analysis from the TRAC-24 randomized control trial

“…TRAC-24 has been described in detail previously. 11 , 12 , 17 In brief, it was a phase IV, single-centre, open label, parallel group RCT. The Northern Ireland clinical trials unit (NICTU) coordinated the trial and four surgeons (DB, see Acknowledgements for others) from Musgrave Park Hospital enrolled their patients.…”

“…The results revealed that extended oral dosing of TXA (1 g IV and then four oral doses over a 24-hour period postoperatively) significantly reduced blood loss in TKA but not THA, compared to a single IV dose or no TXA. 11 , 12 No increase in adverse thromboembolic events was reported despite the inclusion of high-risk patients.…”

Study protocol for discharge on day of surgery after hip and knee arthroplasty from the Center for Fast-track Hip and Knee Replacement

“…All patients receive high-dose glucocorticoids preoperatively (24 mg dexamethasone or 125 mg methylprednisolone) except insulin-dependent diabetic patients (19)(20)(21)(22). 1 gram of tranexamic acid is administered intravenously during surgery in all patients and may be repeated 3-4 hours postoperatively (23,24). Patients are operated on according to a standard protocol of the individual center.…”